In vivo and ex vivo effects of adenosine A1 and A2 receptor agonists on platelet aggregation in the rabbit

Effect of adenosine A2 receptor stimulation on platelet activation–aggregation: Differences between canine and human models

“…In contrast, impedance in matched aliquots pretreated with CGS was significantly reduced to a mean of 12 ohms ( Figure 3B), a finding consistent with previous in vitro data obtained with adenosine A 2 agonists [4,11,12,22] and consistent with the concept that CGS attenuates thrombosis.…”

“…Moreover, release of adenosine from ischemic-reperfused cardiomyocytes has been hypothesized to contribute to the favorable attenuation of recurrent thrombosis evoked by brief antecedent preconditioning ischemia [1][2][3]7,8]. These improvements in patency have been proposed to be a consequence of the welldocumented, platelet inhibitory effects of adenosine, initiated via stimulation of adenosine A 2 receptors on the platelets' surface [1][2][3][4][5][6][8][9][10][11][12]. However, there is at present no direct evidence to substantiate this premise, and the specific site of action of adenosine/adenosine agonists (i.e., stimulation of A 2 receptors on platelets versus other blood-borne elements and/or vascular smooth muscle) has not been established.…”

Dipyridamole, an Underestimated Vascular Protective Drug

“…Since purines are effective inhibitors of the adenosine A2A receptor [15] it was important to study their effects on platelets. However, the hypothesis that the adenosine effect on platelets is also blocked by purines, analogous to the action on blood vessels, was convincingly refuted: experiments with isolated platelets, in experimental animals, in human volunteers and in human coronary patients showed that the anti-aggregating actions of dipyridamole are not blocked by purines and that, on the contrary, the anti-aggregating actions are increased by purines via upregulation of the adenosine A2A receptors [23][24][25].…”

In Vitro Platelet Responsiveness to Adenosine-Mediated ‘Preconditioning’ is Age-Dependent

“…In brief, for each sample, blood aliquots (0.5 mL) were diluted with an equal volume of sterile 0.9% saline and maintained at 37 • C. Matched aliquots from each animal were randomly assigned to receive exogenous treatment with either the adenosine A 2 receptor agonist CGS 21680 (final concentration: 10 µM) or an equivalent volume of saline. The concentration of CGS was chosen on the basis of dose-response studies in our laboratory, and evokes, in multiple species (rat, rabbit, dog and human), a maximal (20-40%) inhibition of in vitro platelet aggregation [30,32]. Nonetheless, to ensure an adequate concentration of the agonist, additional aliquots obtained from 4 year old rabbits and 2 year old rats were treated, in a post-hoc manner, with 20 µM CGS.…”